Skip to main content
SpringerLink
Log in

Pharmacogenomics of G Protein-Coupled Receptor Signaling and Other Pathways in Essential Hypertension

  • Protocol
  • First Online:
G Protein-Coupled Receptor Genetics

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

Essential hypertension represents a cluster of genetically determined physiological abnormalities that is influenced by environmental factors and the individual’s lifestyle. Essential hypertension is a major public health challenge because it affects one in every three adult Americans and about one billion people worldwide, yet its current treatment is empirical and is focused on the remediation of a physical sign (i.e., high blood pressure [BP]) and not the underlying cause. In spite of the demonstrable utility of antihypertensive therapy, less than 50 % of patients are effectively managed. Surmounting the limitations of empirical medicine can be achieved by identifying the genetic variants that predispose an individual to develop hypertension and target organ susceptibility, as well as predict therapeutic efficacy. An increasing number of studies have shown that certain variants of genes that regulate blood pressure, including G protein-coupled receptors (GPCRs), also affect the response to antihypertensive treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Ni X, Zhang W, Huang RS (2012) Pharmacogenomics discovery and implementation in genome-wide association studies era. Wiley Interdiscip Rev Syst Biol Med 5:1–9

    PubMed Central  PubMed  Google Scholar 

  2. Howland RH (2012) Future prospects for pharmacogenetics in the quest for personalized medicine. J Psychosoc Nurs Ment Health Serv 50:13–16

    Google Scholar 

  3. Giacomini KM, Yee SW, Ratain MJ et al (2012) Pharmacogenomics and patient care: one size does not fit all. Sci Transl Med 4:153

    Google Scholar 

  4. Altman RB, Whirl-Carrillo M, Klein TE (2013) Challenges in the pharmacogenomic annotation of whole genomes. Clin Pharmacol Ther 94:211–213

    CAS  PubMed  Google Scholar 

  5. Machalek A (2008) Launching a global alliance for pharmacogenomics. National Institute of General Medical Sciences, NIH News Release, 14 Apr 2008

    Google Scholar 

  6. Arakawa S, Takahashi A, Ashikawa K et al (2011) Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population. Nat Genet 43:1001–1004

    CAS  PubMed  Google Scholar 

  7. Kearney PM, Whelton M, Reynolds K et al (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365:217–223

    PubMed  Google Scholar 

  8. Roger VL, Go AS, Lloyd-Jones D et al (2012) Heart disease and stroke statistics–2012 update: a report from the American Heart Association. Circulation 125:e2–e220

    PubMed  Google Scholar 

  9. Egan BM, Zhao Y, Axon RN (2010) US trends in prevalence, awareness, treatment, and control of hypertension, 1988–2008. JAMA 303:2043–2050

    CAS  PubMed  Google Scholar 

  10. Heidenreich PA, Trogdon JG, Khavjou OA et al (2011) Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation 123:933–944

    PubMed  Google Scholar 

  11. Centers for Disease Control and Prevention (CDC) (2013) Racial/ethnic disparities in the awareness, treatment, and control of hypertension – United States from 2003–2010. MMWR 62:351–355

    Google Scholar 

  12. Roden DM, Johnson JA, Kimmel SE et al (2011) Cardiovascular pharmacogenomics. Circ Res 109:807–820

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Baccarelli A, Ghosh S (2012) Environmental exposures, epigenetics and cardiovascular disease. Curr Opin Clin Nutr Metab Care 15:323–329

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Doris PA (2002) Hypertension genetics, single nucleotide polymorphisms, and the common disease: common variant hypothesis. Hypertension 39:323–331

    CAS  PubMed  Google Scholar 

  15. Harrap SB (2009) Blood pressure genetics: time to focus. J Am Soc Hypertens 3: 231–237

    PubMed  Google Scholar 

  16. Jiang X, Barmada MM, Visweswaran S (2010) Identifying genetic interactions in genome-wide data using Bayesian networks. Genet Epidemiol 34:575–581

    PubMed  Google Scholar 

  17. Basson J, Simino J, Rao DC (2012) Between candidate genes and whole genomes: time for alternative approaches in blood pressure genetics. Curr Hypertens Rep 14:46–61

    PubMed  Google Scholar 

  18. Moore JH, Asselbergs FW, Williams SM (2010) Bioinformatics challenges for genome-wide association studies. Bioinformatics 26: 445–455

    CAS  PubMed  Google Scholar 

  19. Glazier AM, Nadeau JH, Aitman TJ (2002) Finding genes that underlie complex traits. Science 298:2345–2349

    CAS  PubMed  Google Scholar 

  20. Abiola O, Angel JM, Avner P et al (2003) The nature and identification of quantitative trait loci: a community’s view. Nat Rev Genet 4:911–916

    PubMed  Google Scholar 

  21. Hall JE, Granger JP, do Carmo JM et al (2012) Hypertension: physiology and pathophysiology. Compr Physiol 2:2393–2442

    PubMed  Google Scholar 

  22. Doris PA (2008) Promoting regulatory gene variation in sodium reabsorption. Hypertension 52:623–624

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Chiolero A, Maillard M, Nussberger J et al (2001) Proximal sodium reabsorption: an independent determinant of blood pressure response to salt. Hypertension 36:631–637

    Google Scholar 

  24. Ortiz PA, Garvin JL (2001) Intrarenal transport and vasoactive substances in hypertension. Hypertension 38:621–624

    CAS  PubMed  Google Scholar 

  25. Aviv A, Hollenberg NK, Weder A (2004) Urinary potassium excretion and sodium sensitivity in blacks. Hypertension 43:707–713

    CAS  PubMed  Google Scholar 

  26. Strazzullo P, Galletti F, Barba G (2003) Altered renal handling of sodium in human hypertension: short review of the evidence. Hypertension 41:1000–1005

    CAS  PubMed  Google Scholar 

  27. Dahl LK, Heine M, Thompson K (1974) Genetic influence of the kidneys on blood pressure. Evidence from chronic renal homografts in rats with opposite predispositions to hypertension. Circ Res 40:94–101

    CAS  PubMed  Google Scholar 

  28. Morgan DA, DiBona GF, Mark AL (1990) Effects of interstrain renal transplantation on NaCl-induced hypertension in Dahl rats. Hypertension 15:436–442

    CAS  PubMed  Google Scholar 

  29. Crowley SD, Gurley SB, Oliverio MI et al (2005) Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system. J Clin Invest 115:1092–1099

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Asico L, Zhang X, Jiang J et al (2011) Lack of renal dopamine D5 receptors promotes hypertension. J Am Soc Nephrol 22:82–89

    CAS  PubMed  Google Scholar 

  31. Curtis JJ, Luke RG, Dustan HP et al (1983) Remission of essential hypertension after renal transplantation. N Engl J Med 309: 1009–1015

    CAS  PubMed  Google Scholar 

  32. Guidi E, Menghetti D, Milani S et al (1996) Hypertension may be transplanted with the kidney in humans: a long term historical prospective follow up of recipients grafted with kidneys coming from donors with or without hypertension in their families. J Am Soc Nephrol 7:1131–1138

    CAS  PubMed  Google Scholar 

  33. Sander S, Rettig R, Ehrig B (1996) Role of the native kidney in experimental post transplantation hypertension. Pflugers Arch 431: 971–976

    CAS  PubMed  Google Scholar 

  34. DiBona GF (2013) Sympathetic nervous system and hypertension. Hypertension 61: 556–560

    CAS  PubMed  Google Scholar 

  35. Santisteban MM, Zubcevic J, Baekey DM et al (2013) Dysfunctional brain-bone marrow communication: a paradigm shift in the pathophysiology of hypertension. Curr Hypertens Rep 15:377–389

    PubMed  Google Scholar 

  36. Foss JD, Fink GD, Osborn JW (2013) Reversal of genetic salt-sensitive hypertension by targeted sympathetic ablation. Hypertension 61: 806–811

    CAS  PubMed  Google Scholar 

  37. Thomson SP, Stump CS, Kurukulasuriya LR et al (2007) Adrenal steroids and the metabolic syndrome. Curr Hypertens Rep 9:512–519

    CAS  PubMed  Google Scholar 

  38. Schiffrin EL (2012) Vascular remodeling in hypertension: mechanisms and treatment. Hypertension 59:367–374

    CAS  PubMed  Google Scholar 

  39. Titze J, Machnik A (2012) Sodium sensing in the interstitium and relationship to hypertension. Curr Opin Nephrol Hypertens 19: 385–392

    Google Scholar 

  40. Chen K, Keaney JF Jr (2012) Evolving concepts of oxidative stress and reactive oxygen species in cardiovascular disease. Curr Atheroscler Rep 14:476–483

    CAS  PubMed  Google Scholar 

  41. Montezano A, Touyz RM (2013) Reactive oxygen species, vascular Noxs and hypertension: focus on translational and clinical research. Antioxid Redox Signal, 6 June 2013, epub ahead of print

    Google Scholar 

  42. Lu Q, Yang Y, Villar VA et al (2013) D5 dopamine receptor decreases NADPH oxidase, reactive oxygen species and blood pressure via heme oxygenase-1. Hypertens Res 36:684–690

    CAS  PubMed  Google Scholar 

  43. Daiber A (2010) Redox signaling (cross-talk) from and to mitochondria involves mitochondrial pores and reactive oxygen species. Biochim Biophys Acta 1797:897–906

    CAS  PubMed  Google Scholar 

  44. Kozieł R, Pircher H, Kratochwil M et al (2013) Mitochondrial respiratory chain complex I is inactivated by NADPH oxidase Nox4. Biochem J 452:231–239

    PubMed  Google Scholar 

  45. Palm F, Onozato M, Welch WJ et al (2010) Blood pressure, blood flow, and oxygenation in the clipped kidney of chronic 2-kidney, 1-clip rats: effects of tempol and angiotensin blockade. Hypertension 55:298–304

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Banday AA, Lokhandwala MF (2008) Oxidative stress-induced renal angiotensin AT1 receptor upregulation causes increased stimulation of sodium transporters and hypertension. Am J Physiol Renal Physiol 295: F698–F706

    CAS  PubMed  Google Scholar 

  47. Kim SM, Kim YG, Jeong KH et al (2012) Angiotensin II-induced mitochondrial Nox4 is a major endogenous source of oxidative stress in kidney tubular cells. PLoS One 7:e39739

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Yang Y, Zhang Y, Cuevas S et al (2012) Paraoxonase 2 decreases renal reactive oxygen species production, lowers blood pressure, and mediates dopamine D2 receptor-induced inhibition of NADPH oxidase. Free Radic Biol Med 53:437–446

    CAS  PubMed Central  PubMed  Google Scholar 

  49. George LE, Lokhandwala MF, Asghar M (2012) Novel role of NF-κB-p65 in antioxidant homeostasis in human kidney-2 cells. Am J Physiol Renal Physiol 302:F1440–F1446

    CAS  PubMed  Google Scholar 

  50. Schreck C, O’Connor PM (2001) NAD(P)H oxidase and renal epithelial ion transport. Am J Physiol Regul Integr Comp Physiol 300: R1023–R1029

    Google Scholar 

  51. Cosentino F, Patton S, d’Uscio LV et al (1998) Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats. J Clin Invest 101:1530–1537

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Harrison DG, Guzik TJ, Lob HE et al (2011) Inflammation, immunity, and hypertension. Hypertension 57:132–140

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Quiroz Y, Johnson RJ, Rodríguez-Iturbe B (2012) The role of T cells in the pathogenesis of primary hypertension. Nephrol Dial Transplant 27:S2–S5

    Google Scholar 

  54. Segerer S, Schlöndorff D (2007) Role of chemokines for the localization of leukocyte subsets in the kidney. Semin Nephrol 27: 260–274

    CAS  PubMed  Google Scholar 

  55. Schmidt C, Höcherl K, Schweda F et al (2007) Regulation of renal sodium transporters during severe inflammation. J Am Soc Nephrol 18:1072–1083

    CAS  PubMed  Google Scholar 

  56. Vasdev S, Stuckless J, Richardson V (2011) Role of the immune system in hypertension: modulation by dietary antioxidants. Int J Angiol 20:189–212

    PubMed Central  PubMed  Google Scholar 

  57. Johnson JA (2010) Pharmacogenomics of antihypertensive drugs: past, present and future. Pharmacogenomics 11:487–491

    CAS  PubMed  Google Scholar 

  58. Efendiev R, Krmar RT, Ogimoto G et al (2004) Hypertension-linked mutation in the adducin alpha-subunit leads to higher AP2–mu2 phosphorylation and impaired Na+, K + -ATPase trafficking in response to GPCR signals and intracellular sodium. Circ Res 95: 1100–1108

    CAS  PubMed  Google Scholar 

  59. Liu K, Liu J, Huang Y et al (2010) Alpha-adducin Gly460Trp polymorphism and hypertension risk: a meta-analysis of 22 studies including 14303 cases and 15961 controls. PLoS One 5:e13057

    PubMed Central  PubMed  Google Scholar 

  60. Lanzani C, Citterio L, Glorioso N et al (2010) Adducin- and ouabain-related gene variants predict the antihypertensive activity of rostafuroxin, part 2: clinical studies. Sci Transl Med 2:59–87

    Google Scholar 

  61. Staessen JA, Thijs L, Stolarz-Skrzypek K et al (2011) Main results of the Ouabain and Adducin for Specific Intervention on Sodium in Hypertension Trial (OASIS-HT): a randomized placebo-controlled phase-2 dose-finding study of rostafuroxin. Trials 12:13

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Manunta P, Lavery G, Lanzani C et al (2008) Physiological interaction between alpha-adducin and WNK1-NEDD4L pathways on sodium-related blood pressure regulation. Hypertension 52:366–372

    CAS  PubMed  Google Scholar 

  63. Ronzaud C, Loffing-Cueni D, Hausel P et al (2013) Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension. J Clin Invest 123:657–665

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Oberfeld B, Ruffieux-Daidié D, Vitagliano JJ et al (2011) Ubiquitin-specific protease 2–45 (Usp2-45) binds to epithelial Na+ channel (ENaC)-ubiquitylating enzyme Nedd4-2. Am J Physiol Renal Physiol 301:F189–F196

    CAS  PubMed  Google Scholar 

  65. Luo F, Wang Y, Wang X et al (2009) A functional variant of NEDD4L is associated with hypertension, antihypertensive response, and orthostatic hypotension. Hypertension 54: 796–801

    CAS  PubMed  Google Scholar 

  66. Svensson-Färbom P, Wahlstrand B, Almgren P et al (2011) A functional variant of the NEDD4L gene is associated with beneficial treatment response with β-blockers and diuretics in hypertensive patients. J Hypertens 29:388–395

    PubMed  Google Scholar 

  67. Wang XF, Lu XM, Lin RY et al (2008) Lack of association of functional variants in alpha-ENaC gene and essential hypertension in two ethnic groups in China. Kidney Blood Press Res 31:268–273

    CAS  PubMed  Google Scholar 

  68. Poch E, González D, de la Sierra A et al (2000) Genetic variation of the gamma subunit of the epithelial Na + channel and essential hypertension. Relationship with salt sensitivity. Am J Hypertens 13:648–653

    CAS  PubMed  Google Scholar 

  69. Hannila-Handelberg T, Kontula K, Tikkanen I et al (2005) Common variants of the beta and gamma subunits of the epithelial sodium channel and their relation to plasma renin and aldosterone levels in essential hypertension. BMC Med Genet 6:4

    PubMed Central  PubMed  Google Scholar 

  70. Zhao Q, Gu D, Hixson JE et al (2011) Common variants in epithelial sodium channel genes contribute to salt sensitivity of blood pressure: the GenSalt study. Circ Cardiovasc Genet 4:375–380

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Turner ST, Bailey KR, Schwartz GL et al (2012) Genomic association analysis identifies multiple loci influencing antihypertensive response to an angiotensin II receptor blocker. Hypertension 59:1204–1211

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Wang Y, O’Connell JR, McArdle PF et al (2009) Whole-genome association study identifies STK39 as a hypertension susceptibility gene. Proc Natl Acad Sci U S A 106: 226–231

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Adeyemo A, Gerry N, Chen G et al (2009) A genome-wide association study of hypertension and blood pressure in African Americans. PLoS Genet 5:e1000564

    PubMed Central  PubMed  Google Scholar 

  74. Rhee MY, Yang SJ, Oh SW et al (2011) Novel genetic variations associated with salt sensitivity in the Korean population. Hypertens Res 34:606–611

    CAS  PubMed  Google Scholar 

  75. McCormick JA, Mutig K, Nelson JH et al (2011) A SPAK isoform switch modulates renal salt transport and blood pressure. Cell Metab 14:352–364

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Grimm PR, Taneja TK, Liu J et al (2012) SPAK isoforms and OSR1 regulate sodium-chloride co-transporters in a nephron-specific manner. J Biol Chem 287:37673–37690

    CAS  PubMed  Google Scholar 

  77. Bergaya S, Faure S, Baudrie V et al (2011) WNK1 regulates vasoconstriction and blood pressure response to α1-adrenergic stimulation in mice. Hypertension 58:439–445

    CAS  PubMed  Google Scholar 

  78. Castañeda-Bueno M, Cervantes-Pérez LG, Vázquez N et al (2012) Activation of the renal Na+:Cl− cotransporter by angiotensin II is a WNK4-dependent process. Proc Natl Acad Sci U S A 109:7929–7934

    PubMed Central  PubMed  Google Scholar 

  79. Donner KM, Hiltunen TP, Hannila-Handelberg T et al (2012) STK39 variation predicts the ambulatory blood pressure response to losartan in hypertensive men. Hypertens Res 35:107–114

    CAS  PubMed  Google Scholar 

  80. Duarte JD, Lobmeyer MT, Wang Z et al (2010) Lack of association between polymorphisms in STK39, a putative thiazide response gene, and blood pressure response to hydrochlorothiazide. Pharmacogenet Genomics 20:516–519

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Xi B, Shen Y, Reilly KH et al (2013) Recapitulation of four hypertension susceptibility genes (CSK, CYP17A1, MTHFR, and FGF5) in East Asians. Metabolism 62: 196–203

    CAS  PubMed  Google Scholar 

  82. Tabara Y, Kohara K, Kita Y et al (2010) Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japanese Millennium Genome Project. Hypertension 56:973–980

    CAS  PubMed  Google Scholar 

  83. Hanada K, Yewdell JW, Yang JC (2004) Immune recognition of a human renal cancer antigen through post-translational protein splicing. Nature 427:252–256

    CAS  PubMed  Google Scholar 

  84. Sautter NB, Delaney KL, Hausman FA et al (2012) Tissue remodeling gene expression in a murine model of chronic rhinosinusitis. Laryngoscope 122:711–717

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Gong Y, McDonough CW, Wang Z et al (2012) Hypertension susceptibility loci and blood pressure response to antihypertensives: results from the pharmacogenomic evaluation of antihypertensive responses study. Circ Cardiovasc Genet 5:686–691

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Kawasawa Y, McKenzie LM, Hill DP et al (2003) G protein-coupled receptor genes in the FANTOM2 database. Genome Res 13: 1466–1477

    CAS  PubMed  Google Scholar 

  87. Hansen W, Westendorf AM, Toepfer T et al (2010) Inflammation in vivo is modulated by GPR83 isoform-4 but not GPR83 isoform-1 expression in regulatory T cells. Genes Immun 11:357–361

    CAS  PubMed  Google Scholar 

  88. Müller A, Kleinau G, Piechowski CL et al (2013) G-protein coupled receptor 83 (GPR83) signaling determined by constitutive and zinc(II)-induced activity. PLoS One 8:e53347

    PubMed Central  PubMed  Google Scholar 

  89. Navar LG, Kobori H, Prieto MC et al (2011) Intratubular renin-angiotensin system in hypertension. Hypertension 57:355–362

    CAS  PubMed Central  PubMed  Google Scholar 

  90. de Kloet AD, Krause EG, Shi PD et al (2013) Neuroimmune communication in hypertension and obesity: a new therapeutic angle? Pharmacol Ther 138:428–440

    PubMed  Google Scholar 

  91. Osborn JW, Fink GD, Kuroki MT (2011) Neural mechanisms of angiotensin II-salt hypertension: implications for therapies targeting neural control of the splanchnic circulation. Curr Hypertens Rep 13:221–228

    PubMed Central  PubMed  Google Scholar 

  92. Dhande I, Ali Q, Hussain T (2013) Proximal tubule angiotensin AT2 receptors mediate an anti-inflammatory response via interleukin-10: role in renoprotection in obese rats. Hypertension 61:1218–1226

    CAS  PubMed  Google Scholar 

  93. Ferrario CM, Varagic J (2010) The ANG-(1–7)/ACE2/mas axis in the regulation of nephron function. Am J Physiol Renal Physiol 298: F1297–F1305

    CAS  PubMed  Google Scholar 

  94. Padia SH, Carey RM (2013) AT2 receptors: beneficial counter-regulatory role in cardiovascular and renal function. Pflugers Arch 465:99–110

    CAS  PubMed Central  PubMed  Google Scholar 

  95. Johnson AD, Newton-Cheh C, Chasman DI et al (2011) Association of hypertension drug target genes with blood pressure and hypertension in 86,588 individuals. Hypertension 57:903–910

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Sookoian S, Gianotti TF, González CD et al (2007) Association of the C-344T aldosterone synthase gene variant with essential hypertension: a meta-analysis. J Hypertens 25:5–13

    CAS  PubMed  Google Scholar 

  97. Li W, Liu C (2012) The -344C/T polymorphism in the CYP11B2 gene is associated with essential hypertension in the Chinese. J Renin Angiotensin Aldosterone Syst, 30 Nov 2012, epub ahead of print

    Google Scholar 

  98. Alvarez-Madrazo S, Mackenzie SM, Davies E et al (2013) Common polymorphisms in the CYP11B1 and CYP11B2 genes: evidence for a digenic influence on hypertension. Hypertension 61:232–239

    CAS  PubMed  Google Scholar 

  99. Su X, Lee L, Li X et al (2007) Association between angiotensinogen, angiotensin II receptor genes, and blood pressure response to an angiotensin-converting enzyme inhibitor. Circulation 115:725–732

    CAS  PubMed  Google Scholar 

  100. Fan X, Wang Y, Sun K et al (2007) Polymorphisms of ACE2 gene are associated with essential hypertension and antihypertensive effects of captopril in women. Clin Pharmacol Ther 82:187–196

    CAS  PubMed  Google Scholar 

  101. Sun B, Williams JS, Pojoga L et al (2011) Renin gene polymorphism: its relationship to hypertension, renin levels and vascular responses. J Renin Angiotensin Aldosterone Syst 12:564–771

    CAS  PubMed Central  PubMed  Google Scholar 

  102. Konoshita T, Kato N, Fuchs S et al (2009) Genetic variant of the renin-angiotensin system and diabetes influences blood pressure response to angiotensin receptor blockers. Diabetes Care 32:1485–1490

    CAS  PubMed  Google Scholar 

  103. Asghar M, Tayebati SK, Lokhandwala MF et al (2011) Potential dopamine-1 receptor stimulation in hypertension management. Curr Hypertens Rep 13:294–302

    CAS  PubMed  Google Scholar 

  104. Jose PA, Soares-da-Silva P, Eisner GM et al (2010) Dopamine and G protein-coupled receptor kinase 4 in the kidney: role in blood pressure regulation. Biochim Biophys Acta 1802:1259–1266

    CAS  PubMed Central  PubMed  Google Scholar 

  105. Carey RM, Schoeffel CD, Gildea JJ et al (2012) Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter. Hypertension 60: 1359–1366

    CAS  PubMed Central  PubMed  Google Scholar 

  106. Liu C, Xi B (2012) Pooled analyses of the associations of polymorphisms in the GRK4 and EMILIN1 genes with hypertension risk. Int J Med Sci 9:274–279

    PubMed Central  PubMed  Google Scholar 

  107. Bhatnagar V, O’Connor DT, Brophy VH et al (2009) G-protein-coupled receptor kinase 4 polymorphisms and blood pressure response to metoprolol among African Americans: sex-specificity and interactions. Am J Hypertens 22:332–338

    CAS  PubMed Central  PubMed  Google Scholar 

  108. Vandell AG, Lobmeyer MT, Gawronski BE et al (2012) G protein receptor kinase 4 polymorphisms: β-blocker pharmacogenetics and treatment-related outcomes in hypertension. Hypertension 60:957–964

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Rayner B, Ramesar R, Steyn K et al (2012) G-protein-coupled receptor kinase 4 polymorphisms predict blood pressure response to dietary modification in Black patients with mild-to-moderate hypertension. J Hum Hypertens 26:334–339

    CAS  PubMed  Google Scholar 

  110. Sanada H, Yatabe J, Yatabe MS et al (2009) G protein-coupled receptor type 4 gene variants and response to antihypertensive medication. Circulation 120:S1087

    Google Scholar 

  111. Wang Z, Armando I, Asico LD et al (2007) The elevated blood pressure of human GRK4γ A142V transgenic mice is not associated with increased ROS production. Am J Physiol Heart Circ Physiol 292:H2083–H2092

    Google Scholar 

  112. Wang Z, Sanada H, Williams S et al (2009) AT1R dysregulation is crucial in the hypertension of human GRK4 A142V transgenic mice. FASEB J 23:802.7

    Google Scholar 

  113. Qian F, Watnick TJ (1999) Somatic mutation as mechanism for cyst formation in autosomal dominant polycystic kidney disease. Mol Genet Metab 68:237–242

    CAS  PubMed  Google Scholar 

  114. Racusen LC, Fivush BA, Andersson H et al (1991) Culture of renal tubular cells from the urine of patients with nephropathic cystinosis. J Am Soc Nephrol 1:1028–1033

    CAS  PubMed  Google Scholar 

  115. O’Connell DP, Ragsdale NV, Boyd DG et al (1997) Differential human renal tubular responses to dopamine type 1 receptor stimulation are determined by blood pressure status. Hypertension 29:115–122

    PubMed  Google Scholar 

  116. Gildea JJ, Lahiff DT, Van Sciver RE et al (2013) A linear relationship between the ex-vivo sodium mediated expression of two sodium regulatory pathways as a surrogate marker of salt sensitivity of blood pressure in exfoliated human renal proximal tubule cells: the virtual renal biopsy. Clin Chim Acta 421:236–242

    CAS  PubMed  Google Scholar 

  117. Sugamara K, Keaney JF Jr (2011) Reactive oxygen species in cardiovascular disease. Free Radic Biol Med 51:978–992

    Google Scholar 

  118. Buettner GR (2011) Superoxide dismutase in redox biology: the roles of superoxide and hydrogen peroxide. Anticancer Agents Med Chem 11:341–346

    CAS  PubMed Central  PubMed  Google Scholar 

  119. Hazen SL, Heinecke JW (1997) 3-chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima. J Clin Invest 99:2075–2081

    CAS  PubMed Central  PubMed  Google Scholar 

  120. Michell AR, Debnam ES, Unwin RJ (2008) Regulation of renal function by the gastrointestinal tract: potential role of gut-derived peptides and hormones. Annu Rev Physiol 70:379–403

    CAS  PubMed  Google Scholar 

  121. Liu T, Jose PA (2013) Gastrin induces sodium-hydrogen exchanger 3 phosphorylation and mTOR activation via a phosphoinositide 3-kinase-/protein kinase C-dependent but AKT-independent pathway in renal proximal tubule cells derived from a normotensive male human. Endocrinology 154:865–875

    CAS  PubMed  Google Scholar 

  122. Hamlyn JM, Blaustein MP (2013) Salt sensitivity, endogenous ouabain and hypertension. Curr Opin Nephrol Hypertens 22:51–58

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The preparation of this chapter and some of the studies were supported by grants from the National Institutes of Health, HL023081, DK039308, HL074940, HL068686, and HL092196.

Author information

Authors and Affiliations

  1. Division of Nephrology, Departments of Medicine and Physiology, University of Maryland School of Medicine, Baltimore, MD, USA

    Pedro A. Jose

  2. Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    Van Anthony M. Villar & Matthew R. Weir

  3. Department of Pathology, University of Virginia School of Medicine, Charlottesville, VA, USA

    Robin A. Felder

Authors
  1. Pedro A. Jose
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Van Anthony M. Villar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Matthew R. Weir
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robin A. Felder
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Oklahoma State University, Tulsa, Oklahoma, USA

    Craig W. Stevens

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Jose, P.A., Villar, V.A.M., Weir, M.R., Felder, R.A. (2014). Pharmacogenomics of G Protein-Coupled Receptor Signaling and Other Pathways in Essential Hypertension. In: Stevens, C. (eds) G Protein-Coupled Receptor Genetics. Methods in Pharmacology and Toxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-779-2_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-62703-779-2_16

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-778-5

  • Online ISBN: 978-1-62703-779-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation